hydroxysafflor-yellow-a and Dementia--Vascular

Hydroxysafflor yellow A (HSYA) is a drug that exerts angiogenesis regulatory and neuroprotective effects and has become an effective therapy for brain and heart ischemic disorders. There is no definite evidence supporting a therapeutic effect of HSYA in vascular dementia (VaD). We used HSYA in a rat model of chronic cerebral ischemia to determine its potential therapeutic effects in VaD. The Morris water maze (MWM) was used to evaluate spatial cognitive function, and long-term potentiation (LTP) was tested as a marker of synaptic plasticity. The expression levels of brain-derived neurotrophic factor (BDNF) and two subunits of N-methyl-d-aspartate receptor (NMDAR; GluN2A and GluN2B) in the hippocampus were measured via western blotting. The MWM results showed that the experimental VaD group had longer escape latencies than the sham group, whereas the HSYA group had a decreased escape latency compared with the VaD group (P<0.05). The LTP at CA3-CA1 synapses in the hippocampus was also enhanced in the HSYA compared with the VaD group (P<0.05). The western blotting results revealed lower hippocampal BDNF and GluN2B expression in the VaD group compared with the sham group and significantly higher hippocampal expression in the HSYA group compared with the VaD group. No significant change in GluN2A expression was detected. The results indicate that HSYA may enhance the endogenous expression of BDNF and GluN2B, which are associated with the synaptic plasticity of the hippocampus, and may improve spatial learning and memory abilities in a rat model of VaD.

Topics: Angiogenesis Inducing Agents; Animals; Brain-Derived Neurotrophic Factor; Chalcone; Dementia, Vascular; Disease Models, Animal; Drug Evaluation, Preclinical; Hippocampus; Long-Term Potentiation; Male; Maze Learning; Neuroprotective Agents; Nootropic Agents; Quinones; Random Allocation; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Spatial Memory; Up-Regulation

Hydroxysafflor yellow A (HSYA) has angiogenesis-regulating and neuro-protective effects, but its effects on vascular dementia (VaD) are unknown. In this study, 30 adult Sprague-Dawley rats were randomly allocated to five groups: normal, sham-operation, VaD alone (bilateral carotid artery occlusion), VaD plus saline (control), and VaD plus HSYA. One week after operation, the HSYA group received one daily tail-vein injection of 0.6 mg/100 g HSYA for two weeks. Five weeks after operation, the spatial memory of all five groups was evaluated by the water maze task, and synaptic plasticity in the hippocampus was assessed by the long-term potentiation (LTP) method. Vascular endothelial growth factor (VEGF) and N-methyl-Daspartic acid receptor 1 (NR1) expression in the hippocampus was detected via Western blot. We found that, compared with the group with VaD alone, the group with HSYA had a reduced escape latency in the water maze (P < 0.05), and the LTP at CA3-CA1 synapses in the hippocampus was enhanced (P < 0.05). Western blot in the late-phase VaD group showed slight up-regulation of VEGF and downregulation of NR1 in the hippocampus, while HSYA significantly up-regulated both VEGF and NR1. These results suggested that HSYA promotes angiogenesis and increases synaptic plasticity, thus improving spatial learning and memory in the rat model of VaD.

Topics: Animals; Carotid Artery Diseases; Chalcone; Dementia, Vascular; Disease Models, Animal; Electric Stimulation; Gene Expression Regulation; Hippocampus; Learning Disabilities; Long-Term Potentiation; Male; Maze Learning; Memory Disorders; Quinones; Random Allocation; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, N-Methyl-D-Aspartate; Time Factors; Vascular Endothelial Growth Factor A